A stable gene selection in microarray data analysis.
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ABSTRACT: Background
Microarray data analysis is notorious for involving a huge number of genes compared to a relatively small number of samples. Gene selection is to detect the most significantly differentially expressed genes under different conditions, and it has been a central research focus. In general, a better gene selection method can improve the performance of classification significantly. One of the difficulties in gene selection is that the numbers of samples under different conditions vary a lot.Results
Two novel gene selection methods are proposed in this paper, which are not affected by the unbalanced sample class sizes and do not assume any explicit statistical model on the gene expression values. They were evaluated on eight publicly available microarray datasets, using leave-one-out cross-validation and 5-fold cross-validation. The performance is measured by the classification accuracies using the top ranked genes based on the training datasets.Conclusion
The experimental results showed that the proposed gene selection methods are efficient, effective, and robust in identifying differentially expressed genes. Adopting the existing SVM-based and KNN-based classifiers, the selected genes by our proposed methods in general give more accurate classification results, typically when the sample class sizes in the training dataset are unbalanced.
SUBMITTER: Yang K
PROVIDER: S-EPMC1524991 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The number of genes declared differentially expressed is a random variable and its variability can be assessed by resampling techniques. Another important stability indicator is the frequency with which a given gene is selected across subsamples. We have conducted studies to assess stability and some other properties of several gene selection procedures with biological and simulated data.Using resampling techniques we have found that some genes are selected much less frequently (across sub-samples) than other genes with the same adjusted p-values. The extent to which this type of instability manifests itself can be assessed by a method introduced in this paper. The effect of correlation between gene expression levels on the performance of multiple testing procedures is studied by computer simulations.Resampling represents a tool for reducing the set of initially selected genes to those with a sufficiently high selection frequency. Using resampling techniques it is also possible to assess variability of different performance indicators. Stability properties of several multiple testing procedures are described at length in the present paper.
| S-EPMC1403808 | biostudies-other
Project description:BackgroundA common task in microarray data analysis is to identify informative genes that are differentially expressed between two different states. Owing to the high-dimensional nature of microarray data, identification of significant genes has been essential in analyzing the data. However, the performances of many gene selection techniques are highly dependent on the experimental conditions, such as the presence of measurement error or a limited number of sample replicates.ResultsWe have proposed new filter-based gene selection techniques, by applying a simple modification to significance analysis of microarrays (SAM). To prove the effectiveness of the proposed method, we considered a series of synthetic datasets with different noise levels and sample sizes along with two real datasets. The following findings were made. First, our proposed methods outperform conventional methods for all simulation set-ups. In particular, our methods are much better when the given data are noisy and sample size is small. They showed relatively robust performance regardless of noise level and sample size, whereas the performance of SAM became significantly worse as the noise level became high or sample size decreased. When sufficient sample replicates were available, SAM and our methods showed similar performance. Finally, our proposed methods are competitive with traditional methods in classification tasks for microarrays.ConclusionsThe results of simulation study and real data analysis have demonstrated that our proposed methods are effective for detecting significant genes and classification tasks, especially when the given data are noisy or have few sample replicates. By employing weighting schemes, we can obtain robust and reliable results for microarray data analysis.
| S-EPMC5581932 | biostudies-literature
Project description:A random forest method has been selected to perform both gene selection and classification of the microarray data. In this embedded method, the selection of smallest possible sets of genes with lowest error rates is the key factor in achieving highest classification accuracy. Hence, improved gene selection method using random forest has been proposed to obtain the smallest subset of genes as well as biggest subset of genes prior to classification. The option for biggest subset selection is done to assist researchers who intend to use the informative genes for further research. Enhanced random forest gene selection has performed better in terms of selecting the smallest subset as well as biggest subset of informative genes with lowest out of bag error rates through gene selection. Furthermore, the classification performed on the selected subset of genes using random forest has lead to lower prediction error rates compared to existing method and other similar available methods.
| S-EPMC3218317 | biostudies-literature
Project description:BackgroundSelection of relevant genes for sample classification is a common task in most gene expression studies, where researchers try to identify the smallest possible set of genes that can still achieve good predictive performance (for instance, for future use with diagnostic purposes in clinical practice). Many gene selection approaches use univariate (gene-by-gene) rankings of gene relevance and arbitrary thresholds to select the number of genes, can only be applied to two-class problems, and use gene selection ranking criteria unrelated to the classification algorithm. In contrast, random forest is a classification algorithm well suited for microarray data: it shows excellent performance even when most predictive variables are noise, can be used when the number of variables is much larger than the number of observations and in problems involving more than two classes, and returns measures of variable importance. Thus, it is important to understand the performance of random forest with microarray data and its possible use for gene selection.ResultsWe investigate the use of random forest for classification of microarray data (including multi-class problems) and propose a new method of gene selection in classification problems based on random forest. Using simulated and nine microarray data sets we show that random forest has comparable performance to other classification methods, including DLDA, KNN, and SVM, and that the new gene selection procedure yields very small sets of genes (often smaller than alternative methods) while preserving predictive accuracy.ConclusionBecause of its performance and features, random forest and gene selection using random forest should probably become part of the "standard tool-box" of methods for class prediction and gene selection with microarray data.
| S-EPMC1363357 | biostudies-literature
Project description:In cancer studies, it is common that multiple microarray experiments are conducted to measure the same clinical outcome and expressions of the same set of genes. An important goal of such experiments is to identify a subset of genes that can potentially serve as predictive markers for cancer development and progression. Analyses of individual experiments may lead to unreliable gene selection results because of the small sample sizes. Meta analysis can be used to pool multiple experiments, increase statistical power, and achieve more reliable gene selection. The meta analysis of cancer microarray data is challenging because of the high dimensionality of gene expressions and the differences in experimental settings amongst different experiments.We propose a Meta Threshold Gradient Descent Regularization (MTGDR) approach for gene selection in the meta analysis of cancer microarray data. The MTGDR has many advantages over existing approaches. It allows different experiments to have different experimental settings. It can account for the joint effects of multiple genes on cancer, and it can select the same set of cancer-associated genes across multiple experiments. Simulation studies and analyses of multiple pancreatic and liver cancer experiments demonstrate the superior performance of the MTGDR.The MTGDR provides an effective way of analyzing multiple cancer microarray studies and selecting reliable cancer-associated genes.
| S-EPMC2631520 | biostudies-literature
Project description:BackgroundThe wealth of gene expression values being generated by high throughput microarray technologies leads to complex high dimensional datasets. Moreover, many cohorts have the problem of imbalanced classes where the number of patients belonging to each class is not the same. With this kind of dataset, biologists need to identify a small number of informative genes that can be used as biomarkers for a disease.ResultsThis paper introduces a Balanced Iterative Random Forest (BIRF) algorithm to select the most relevant genes for a disease from imbalanced high-throughput gene expression microarray data. Balanced iterative random forest is applied on four cancer microarray datasets: a childhood leukaemia dataset, which represents the main target of this paper, collected from The Children's Hospital at Westmead, NCI 60, a Colon dataset and a Lung cancer dataset. The results obtained by BIRF are compared to those of Support Vector Machine-Recursive Feature Elimination (SVM-RFE), Multi-class SVM-RFE (MSVM-RFE), Random Forest (RF) and Naive Bayes (NB) classifiers. The results of the BIRF approach outperform these state-of-the-art methods, especially in the case of imbalanced datasets. Experiments on the childhood leukaemia dataset show that a 7% ∼ 12% better accuracy is achieved by BIRF over MSVM-RFE with the ability to predict patients in the minor class. The informative biomarkers selected by the BIRF algorithm were validated by repeating training experiments three times to see whether they are globally informative, or just selected by chance. The results show that 64% of the top genes consistently appear in the three lists, and the top 20 genes remain near the top in the other three lists.ConclusionThe designed BIRF algorithm is an appropriate choice to select genes from imbalanced high-throughput gene expression microarray data. BIRF outperforms the state-of-the-art methods, especially the ability to handle the class-imbalanced data. Moreover, the analysis of the selected genes also provides a way to distinguish between the predictive genes and those that only appear to be predictive.
| S-EPMC3766035 | biostudies-literature
Project description:The microarray technique has become a standard means in simultaneously examining expression of all genes measured in different circumstances. As microarray data are typically characterized by high dimensional features with a small number of samples, feature selection needs to be incorporated to identify a subset of genes that are meaningful for biological interpretation and accountable for the sample variation. In this article, we present a simple, yet effective feature selection framework suitable for two-dimensional microarray data. Our correlation-based, nonparametric approach allows compact representation of class-specific properties with a small number of genes. We evaluated our method using publicly available experimental data and obtained favorable results.
| S-EPMC2951666 | biostudies-literature
Project description:BackgroundAccurate diagnosis of cancer subtypes remains a challenging problem. Building classifiers based on gene expression data is a promising approach; yet the selection of non-redundant but relevant genes is difficult. The selected gene set should be small enough to allow diagnosis even in regular clinical laboratories and ideally identify genes involved in cancer-specific regulatory pathways. Here an entropy-based method is proposed that selects genes related to the different cancer classes while at the same time reducing the redundancy among the genes.ResultsThe present study identifies a subset of features by maximizing the relevance and minimizing the redundancy of the selected genes. A merit called normalized mutual information is employed to measure the relevance and the redundancy of the genes. In order to find a more representative subset of features, an iterative procedure is adopted that incorporates an initial clustering followed by data partitioning and the application of the algorithm to each of the partitions. A leave-one-out approach then selects the most commonly selected genes across all the different runs and the gene selection algorithm is applied again to pare down the list of selected genes until a minimal subset is obtained that gives a satisfactory accuracy of classification. The algorithm was applied to three different data sets and the results obtained were compared to work done by others using the same data sets.ConclusionThis study presents an entropy-based iterative algorithm for selecting genes from microarray data that are able to classify various cancer sub-types with high accuracy. In addition, the feature set obtained is very compact, that is, the redundancy between genes is reduced to a large extent. This implies that classifiers can be built with a smaller subset of genes.
| S-EPMC1087831 | biostudies-literature
Project description:This paper introduces a novel approach to gene selection based on a substantial modification of analytic hierarchy process (AHP). The modified AHP systematically integrates outcomes of individual filter methods to select the most informative genes for microarray classification. Five individual ranking methods including t-test, entropy, receiver operating characteristic (ROC) curve, Wilcoxon and signal to noise ratio are employed to rank genes. These ranked genes are then considered as inputs for the modified AHP. Additionally, a method that uses fuzzy standard additive model (FSAM) for cancer classification based on genes selected by AHP is also proposed in this paper. Traditional FSAM learning is a hybrid process comprising unsupervised structure learning and supervised parameter tuning. Genetic algorithm (GA) is incorporated in-between unsupervised and supervised training to optimize the number of fuzzy rules. The integration of GA enables FSAM to deal with the high-dimensional-low-sample nature of microarray data and thus enhance the efficiency of the classification. Experiments are carried out on numerous microarray datasets. Results demonstrate the performance dominance of the AHP-based gene selection against the single ranking methods. Furthermore, the combination of AHP-FSAM shows a great accuracy in microarray data classification compared to various competing classifiers. The proposed approach therefore is useful for medical practitioners and clinicians as a decision support system that can be implemented in the real medical practice.
| S-EPMC4378968 | biostudies-literature
Project description:BackgroundMicroarray devices permit a genome-scale evaluation of gene function. This technology has catalyzed biomedical research and development in recent years. As many important diseases can be traced down to the gene level, a long-standing research problem is to identify specific gene expression patterns linking to metabolic characteristics that contribute to disease development and progression. The microarray approach offers an expedited solution to this problem. However, it has posed a challenging issue to recognize disease-related genes expression patterns embedded in the microarray data. In selecting a small set of biologically significant genes for classifier design, the nature of high data dimensionality inherent in this problem creates substantial amount of uncertainty.ResultsHere we present a model for probability analysis of selected genes in order to determine their importance. Our contribution is that we show how to derive the P value of each selected gene in multiple gene selection trials based on different combinations of data samples and how to conduct a reliability analysis accordingly. The importance of a gene is indicated by its associated P value in that a smaller value implies higher information content from information theory. On the microarray data concerning the subtype classification of small round blue cell tumors, we demonstrate that the method is capable of finding the smallest set of genes (19 genes) with optimal classification performance, compared with results reported in the literature.ConclusionIn classifier design based on microarray data, the probability value derived from gene selection based on multiple combinations of data samples enables an effective mechanism for reducing the tendency of fitting local data particularities.
| S-EPMC1274261 | biostudies-literature